Improvement of Hemodialysis Catheter Function with Tenecteplase: A Phase III, Open-Label Study: TROPICS 4

Abstract

Hemodialysis (HD) catheters are prone to thrombotic occlusion. We evaluated tenecteplase, a thrombolytic, for the treatment of dysfunctional HD catheters. Patients with tunneled HD catheters and blood flow rate (BFR) <300 mL/min received open-label tenecteplase (2 mg/lumen) for a 1 h intracatheter dwell. Treatment success was defined as BFR ≥ 300 mL/min and a ≥ 25 mL/min increase from baseline BFR, 30 min before and at the end of HD. Patients without treatment success at the end of the initial visit received another 2 mg dose of tenecteplase for an up to 72 h extended dwell. Of 223 enrolled patients, 34% (95% confidence interval [CI], 28-40%) had treatment success after a 1 h dwell. Mean (standard deviation [SD]) BFR change from baseline was 82 (124) mL/min. Treatment success in those who received extended-dwell tenecteplase (n = 116) was 49% (95% CI, 40-58%), with mean (SD) BFR change from baseline of 117 (140) mL/min. Reported targeted adverse events included five catheter-related bloodstream infections and one thrombosis. No intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications were reported. Tenecteplase administered as a 1 h or 1 h plus extended dwell was associated with improved HD catheter function in the TROPICS 4 trial.

Efficacy, Safety, and Cost of Thrombolytic Agents for the Management of Dysfunctional Hemodialysis Catheters: A Systematic Review

“…The largest number of studies and the greatest number of catheter treatment episodes were reported with alteplase (Table 1). [22][23][24][25][26][27][28][29][30][31][32][33] Although 37 lumen fails, repeat treatment ability to complete once hemodialysis 39 was instilled with before and at end a dwell time of of dialysis up to 72 hrs TROPICS = Tenecteplase for the restoration of function in dysfunctional hemodialysis catheters. (Table 3), the numbers of catheter treatment episodes were roughly equal for reteplase and tenecteplase.…”

“…(Table 3), the numbers of catheter treatment episodes were roughly equal for reteplase and tenecteplase. [34][35][36][37][38][39] The number of patients receiving reteplase was about half and the number receiving tenecteplase was about three quarters the number of patients receiving alteplase (406 patients; Table 4).…”

“…Of these articles, only 18 met the inclusion criteria. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Review articles, position statements from KDOQI, studies in patients with catheters for indications other than hemodialysis, studies using only urokinase or streptokinase, and studies failing to adequately describe the methods or outcomes of the use of thrombolytics were excluded.…”

“…In the studies with reteplase and tenecteplase, only dwell protocols were used, and most allowed administration of a second dose if catheter function was not restored after the initial dose. [34][35][36][37][38][39] In the 12 studies with alteplase included in this review, a variety of treatment protocols were used, including push protocols with normal saline after an initial catheter instillation of thrombolytic, continuous infusions, and short-and longduration dwell protocols. [22][23][24][25][26][27][28][29][30][31][32][33] Despite the use of different protocols with alteplase, there was no evidence that one type of protocol was more effective than another.…”

Interventional Nephrology

“…Although the authors found no improvement in thrombosis-free survival, they observed that an international normalized ratio , 1 was significantly associated with a higher rate of tunneled catheter malfunction (37). The TROPICS (Tenecteplase for the Restoration of Function in Dysfunctional HD Catheters) study evaluated tenecteplase, a newer thrombolytic, in dysfunctional catheters in initially 1-hour, and subsequently extended (72-hour), dwells (38). Use of this agent was associated with improved catheter patency and function.…”